A study led in part by Penn scientists examined the DNA of over 10,500 Pakistanis in order to guide research on treatments for heart disease.
Many drugs developed to lower heart disease have targeted a gene linked to arterial plaque, Science Magazine explained. But this study found that the absence of this gene may not greatly affect one's risk for heart disease.
Instead, the study found that the absence of a different gene — called APOC3 — might help.
Penn professor Danish Saleheen and other researchers searched Pakistan for individuals missing a functional copy of the gene. Many Pakistanis marry their first cousins, so parents more frequently pass on identical copies of a gene to their children — meaning that they're also more likely to pass on two nonfunctional copies.
People with these deficient copies of a gene are known as genetic “knockouts,” Philly.com explained. Scientists can deliberately breed animals to produce knockouts, but they must survey large numbers of people to find them in humans.
The researchers found a man, woman and their nine children in Pakistan who were all APOC3 knockouts.
When they consumed a high-fat meal, study participants without functioning APOC3 genes did not experience elevated levels of plasma triglycerides, according to Penn Medicine. Higher levels of triglycerides are a biomarker of heart disease risk.
The family seemed healthy otherwise, which could suggest that missing the function of the APOC3 gene could help treat heart disease without other, harmful effects, Science Magazine noted.
Saleheen told Penn Medicine that these were the world’s first APOC3 knockouts found. He’s been working in Pakistan for over 10 years, amassing as many blood samples as possible, to identify different genetic knockouts — so far he’s found over 1,300 — in over 70,000 participants, a figure he hopes will eventually surpass 200,000 as the work continues.
The study was led by Penn's Perelman School of Medicine, the Center For Non-Communicable Diseases in Pakistan, the Broad Institute of MIT and Harvard and the University of Cambridge.
Co-senior author of the study Sekar Kathiresan told Science Magazine that he hopes this work will lead to a "Human Knockout Project," similar in caliber to the Human Genome Project, in order to aggregate data on knockouts.